Novel compound heterozygous missense mutations in cause Charcot-Marie-Tooth type 4A.

Homozygous or compound heterozygous mutations in the gene cause Charcot-Marie-Tooth (CMT4A) that are consistent with an autosomal recessive mode of inheritance. The case reported in this study is clinically and genetically diagnosed with recessive CMT4A that is caused by a compound novel heterozygous mutation. The genomic DNA of the proband with the clinical diagnosis of CMT was screened for mutations using a targeted next-generation sequencing (NGS) gene-panel that comprised of 27 CMT genes. Two novel compound heterozygous amino acid changing variants were identified in the gene, c.246C>G p.His82Gln in exon 2 and c.614T>G p.Leu205Trp in exon 5. The two amino acid changing variants were not previously reported in the 1000 Genome, Mutation Taster and gnomAD. Our findings expand the phenotypic characterization of the two novel heterozygous mutations associated with CMT4A (AR-CMT1A) and add to the repertoire of mutations related to autosomal recessive CMT in Chinese populations.